Bimoptic plus eye drops 0.3mg / ml, 3ml

Decrease in intraocular pressure in patients with open-angle glaucoma and intraocular hypertension with insufficient effectiveness of local administration of drugs of the group of beta-blockers and prostaglandin analogues.

The recommended dose in adults (including elderly patients) is 1 drop into the conjunctival sac of the affected eye 1 time / day, in the morning or in the evening.

The drug should be used daily at the same time. According to the available literature data on the use of a fixed combination of bimatoprost + timolol, it is assumed that the use of the drug in the evening is more effective in lowering intraocular pressure than the use in the morning. However, the possibility of following the chosen mode of application should be considered. If the administration of the drug is missed, the drug should be administered the next day. It is not recommended to exceed the dose - 1 injection 1 time / day. If more than two drugs are used at the same time, it is necessary to take a 5-minute break between instillations. When pressing on the area of ??the nasolacrimal canal or when closing the eyelids for 2 minutes after instillation of the drug, systemic absorption decreases, which can reduce the risk of side effects and increase the local effect.

Eye drops in the form of a clear solution from colorless to light yellow.

1 ml

bimatoprost 0.3 mg

timolol maleate 6.8 mg,

this corresponds to a timolol content of 5 mg

Excipients: citric acid monohydrate - 0.14 mg, sodium hydrogen phosphate heptahydrate - 2.68 mg, sodium chloride - 6.8 mg, benzalkonium chloride - 0.05 mg, 1M sodium hydroxide solution or 1M hydrochloric acid solution - up to pH 7.3 ± 0.1, purified water - up to 1 ml.

• Syndrome of increased airway reactivity, including bronchial asthma in the acute stage and previous episodes in history;

• severe chronic obstructive pulmonary disease (COPD);

• sinus bradycardia, SSSU, sinoauricular block, II and III degree AV block without an implanted artificial pacemaker;

• clinically significant heart failure;

• cardiogenic shock; age under 18;

• hypersensitivity to the components of the drug.

  With caution: impaired liver and kidney function (the drug has not been studied enough in this category of patients); the presence of risk factors for macular edema (for example, with aphakia, pseudophakia, rupture of the posterior capsule of the lens, as well as intraocular surgery, retinal vein occlusion, inflammatory eye diseases and diabetic retinopathy); active intraocular inflammation (for example, uveitis), because its strengthening is possible; COPD mild to moderate, and only in cases where the expected benefit outweighs the possible risk; AV block I degree due to a negative effect on the time of intracardiac conduction; diseases of the cornea, because the drug can induce dry eye syndrome; diabetes mellitus (unstable course) and impaired glucose tolerance,since the beta-blocker timolol, which is part of the drug, can mask the signs of hypoglycemia; inflammatory changes in the eyes, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma (no data on efficacy and safety studies).

pharmachologic effect

Bimatoprost and timolol, which are part of the drug, reduce intraocular pressure due to combined interaction, leading to a significantly more pronounced hypotensive effect compared to the effect of each of the components separately. Bimatoprost belongs to synthetic prostamides, in chemical structure it is similar to prostaglandin F2-alpha (PGF2?). Bimatoprost does not affect any of the known types of prostaglandin receptors. The hypotensive effect of bimatoprost is carried out by increasing the outflow of intraocular fluid through the trabecula and along the uveoscleral pathway of the eye. Timolol is a non-selective beta-blocker that does not have internal sympathomimetic and membrane-stabilizing activity. Timolol reduces intraocular pressure by reducing the formation of intraocular fluid. The exact mechanism of action has not been established.Perhaps it is associated with inhibition of the synthesis of cyclic adenosine monophosphate (cAMP) and is caused by endogenous stimulation of ?-adrenergic receptors.

Pharmacokinetics

Bimatoprost + timolol

Systemic absorption of the bimatoprost + timolol combination is minimal, it does not differ both in combination treatment and in the instillation of each of the components of the drug separately. In two studies lasting 12 months, there was no systemic cumulation of any of the active ingredients.

Bimatoprost

Suction

In vitro studies have shown that bimatoprost penetrates into the iris and sclera. When a 0.03% solution of bimatoprost is instilled, 1 drop in both eyes 1 time / day for 2 weeks, Cmax of bimatoprost in blood plasma is reached within 10 minutes after application, and within 1.5 hours the concentration in blood plasma decreases to the lower limit of detection (0.025 ng / ml). The average values ??of Cmax and AUC0-24h of bimatoprost were close on days 7 and 14 of application and amounted to 0.08 ng / ml and 0.09 ng h / ml, respectively, indicating that Css of bimatoprost is achieved during the first week of use.

Distribution

Bimatoprost is moderately distributed in tissues, the systemic Vd when the Css of the drug reaches 0.67 l / kg. Bimatoprost is found mainly in blood plasma. Plasma protein binding of bimatoprost is approximately 88%.

Metabolism

Bimatoprost undergoes oxidation, N-deethylation and glucuronidation to form various metabolites.

Withdrawal

Bimatoprost is excreted primarily by the kidneys. About 67% of the drug administered intravenously to healthy volunteers was excreted by the kidneys, and 25% through the intestines. T1 / 2 of bimatoprost, determined after its IV administration, was approximately 45 minutes; and the total clearance is 1.5 l / h / kg.

Pharmacokinetics in special patient groups

When using bimatoprost 2 times / day, the average AUC0-24h in elderly patients is 0.0634 ng h / ml, which significantly exceeds the value of this indicator in healthy young people - 0.0218 ng h / ml. Nevertheless, this difference has no clinical significance, since the systemic exposure of bimatoprost, when applied topically in elderly patients and healthy young people, remains very low. Cumulation of bimatoprost in the systemic circulation is not observed, the safety profile does not differ in elderly patients and young people.

Timolol

Absorption and distribution In patients who underwent surgical treatment of cataracts, after instillation of eye drops in the form of a 0.5% solution, the Cmax of timolol in the intraocular fluid after 1 hour was 898 ng / ml. A certain amount of timolol enters the systemic circulation. Timolol binds to a small extent with blood plasma proteins. Metabolism Timolol, which has entered the systemic circulation, is metabolized in the liver. Excretion of T1 / 2 timolol is about 4-6 hours. Part of timolol, which has undergone metabolism in the liver, is excreted through the intestine, and the other part and metabolites are excreted by the kidneys.

Side effect

Immune system disorders: frequency unknown - hypersensitivity reactions, including signs or symptoms of allergic dermatitis, angioedema, allergic eye reactions. From the side of the psyche: the frequency is unknown - insomnia, nightmares. From the nervous system: often - headache, dizziness; frequency unknown - dysgeusia. From the side of the organ of vision: very often - conjunctival hyperemia; often - punctate keratitis, corneal erosion, burning sensation, itchy eyes, tingling sensation in the eyes, foreign body sensation, dry eyes, redness of the eyelids, eye pain, photophobia, discharge from the eyes, blurred vision, itching of the eyelid skin, decreased visual acuity , blepharitis, eyelid edema, irritation of the mucous membrane of the eyes, increased tearing, eyelash growth; infrequently - iridocyclitis, conjunctival edema, soreness of the eyelids, asthenopia,trichiasis, iris hyperpigmentation, deepening of the eyelid fold, eyelid retraction; frequency unknown - cystic macular edema, eye edema, blurred vision. From the side of the cardiovascular system: the frequency is unknown - bradycardia. From the respiratory system: often - rhinitis; infrequently - dyspnea; frequency unknown - bronchospasm (mainly in patients with existing bronchospastic disease), asthma. Skin and subcutaneous tissue disorders: often - eyelid skin pigmentation, hirsutism, skin hyperpigmentation (periocular); frequency unknown - alopecia. Others: frequency unknown - fatigue. Like other topical ophthalmic drugs, Bimoptic Plus (bimatoprost / timolol) is absorbed into the systemic circulation. The absorption of timolol can cause unwanted effects,similar to the effects of beta-blockers for systemic use. The number of systemic adverse reactions after topical application is lower than after systemic use. Other adverse reactions that were observed with the use of each of the components of the drug (bimatoprost or timolol) and potentially possible during the period of treatment with Bimoptic Plus are presented below. From the immune system: systemic allergic reactions, including anaphylaxis 1. From the side of metabolism: hypoglycemia 1. Mental disorders: depression1, memory loss1. From the nervous system: fainting1, acute cerebrovascular accident1, increased signs and symptoms of myasthenia gravis1, paresthesia1, cerebral ischemia1. From the side of the organ of vision: decreased sensitivity of the cornea1, diplopia1, ptosis1,detachment of the choroid (after surgical treatment of glaucoma) 1, keratitis1, blepharospasm2, retinal hemorrhage2, uveitis2. From the side of the cardiovascular system: AV block1, cardiac arrest1, cardiac arrhythmias1, heart failure1, congestive heart failure1, chest pain1, palpitations1, edema1; decrease in blood pressure1, increase in blood pressure2, Raynaud's syndrome1, cold extremities1. From the respiratory system: exacerbation of asthma2, exacerbation of COPD2, cough1. From the digestive system: nausea1 diarrhea1, dyspepsia1, dryness of the oral mucosa1, abdominal pain1, vomiting1. On the part of the skin and subcutaneous tissues: psoriasis-like rash1 or exacerbation of psoriasis1, skin rash1. From the musculoskeletal system: muscle pain 1. On the part of the genitals and mammary gland: sexual dysfunction1, decreased libido1.General disorders and disorders at the injection site: asthenia 1.2. Laboratory and instrumental data: changes in the activity of liver enzymes 2. 1 Adverse reactions noted during therapy with timolol. 2 Adverse reactions noted with bimatoprost therapy. Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients with significant corneal damage.Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients with significant corneal damage.Adverse reactions to phosphate-containing eye drops Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients with significant corneal damage.

Application during pregnancy and lactation

Pregnancy There are no adequate and well-controlled studies of the fixed combination of bimatoprost + timolol in pregnant women. During pregnancy, the drug should be used only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. In animal studies, data on reproductive toxicity were obtained when using bimatoprost in high doses. Epidemiological studies did not reveal congenital malformations of the fetus, but they established the risk of intrauterine growth retardation when taking drugs from the group of beta-blockers orally. In cases where the patients took a beta-blocker before delivery, the newborns showed clinical symptoms characteristic of this group of drugs (for example, bradycardia, arterial hypotension,respiratory distress syndrome and hypoglycemia). In the case of using the drug Bimoptik Plus until delivery, it is necessary to monitor the condition of the newborn during the first days of life. In animal studies, the reproductive toxicity of timolol has been shown when used in doses significantly higher than those prescribed in clinical practice. Thus, you should not use the drug Bimoptic Plus during pregnancy, except in cases of special need.except in cases of special need.except in cases of special need.

Breastfeeding period

Beta-blockers pass into breast milk. However, when using timolol in the form of eye drops in therapeutic doses, the development of clinical symptoms in children is unlikely, due to the lack of a sufficient amount of the drug in breast milk. It is not known whether bimatoprost passes into human breast milk, but it has been established that it is found in the milk of lactating rats. The drug Bimoptic Plus should not be used in women during breastfeeding.

Application for violations of liver function

The drug should be used with caution in case of liver dysfunction (the drug has not been sufficiently studied in this category of patients).

Application for impaired renal function

The drug should be used with caution in case of impaired renal function (the drug has not been studied enough in this category of patients).

special instructions

Just like other ophthalmic drugs, Bimoptic Plus can enter the systemic circulation. Due to the presence of timolol, a beta-adrenergic component, various types of adverse reactions (from the cardiovascular, respiratory system and other systems) can be observed, as with the use of systemic beta-blockers. The incidence of adverse reactions with topical application of the drug is lower than with systemic use. Cardiovascular system In patients with cardiovascular diseases (such as coronary artery disease, Prinzmetal's angina and heart failure) and during antihypertensive therapy with beta-blockers, it is necessary to evaluate the feasibility of therapy with a combination of bimatoprost + timolol, the use of other drugs should be considered.It is necessary to monitor the condition of patients with cardiovascular diseases to monitor for signs of worsening of these diseases and adverse reactions. Patients with severe peripheral circulatory disorders (for example, severe forms of Raynaud's disease or Raynaud's syndrome) should be used with caution.

Respiratory system

Reported reactions from the respiratory system, including deaths due to bronchospasm in patients with bronchial asthma, after the use of some ophthalmic beta-blockers.

Endocrine system

Beta-blockers can mask the symptoms of hypoglycemia, hyperthyroidism. Other beta-blockers Timolol may affect intraocular pressure or enhance the effect of systemic beta-blockers in patients already receiving a beta-blocker for systemic use. Close monitoring of such patients is recommended. The simultaneous appointment of two beta-blockers for topical use is not recommended.

Anaphylactic reactions

In patients with atopic manifestations in history and severe anaphylactic reactions to various allergens, doses of epinephrine (adrenaline), which are usually used to relieve anaphylactic reactions, may be ineffective with the use of beta-blockers. Choroidal detachment

Cases of choroidal detachment have been reported with the use of therapy that reduces the flow of intraocular fluid (eg, timolol, acetazolamide) after filtration surgery. Anesthesia for surgical procedures Beta-blocking ophthalmic drugs can suppress the systemic effects of beta-agonists such as epinephrine (adrenaline). It is necessary to warn the anesthesiologist about the use of timolol by the patient.

Liver function

In patients with mild liver disease or initially elevated liver enzymes (ALT, ACT) and / or total bilirubin, bimatoprost had no effect on liver function over a study period longer than 24 months. There are no data on adverse reactions due to the effect of timolol on liver function.

Organ of vision

Before starting treatment, patients should be informed about the possible growth of eyelashes, increased pigmentation of the eyelid skin and pigmentation of the iris of the eyes, since these side effects were established in the course of studies of bimatoprost and the fixed combination of bimatoprost + timolol. Some changes may be permanent, may be accompanied by the appearance of differences between the eyes, if the instillation of the drug was carried out in only one eye. After discontinuation of the drug Bimoptic Plus, the pigmentation of the iris may persist. After 12 months of treatment with a fixed combination of bimatoprost + timolol, the frequency of iris pigmentation was noted in 0.2% of patients, and after 12 months of treatment with bimatoprost alone in the form of eye drops - in 1.5%. A further increase in the frequency of this effect was not observed during therapy for 3 years.Increased pigmentation in the iris is due to increased production of melanocytes, not just an increase in their number. The duration of the development of the effect of enhancing the pigmentation of the iris is unknown. The iris discoloration seen with bimatoprost may be subtle over a period from several months to several years. The use of the drug has no effect on nevi or pigment deposits on the iris. Periorbital pigmentation has been reported to be reversible in some patients. A change in refraction is possible (due to the cancellation of therapy with miotic agents in some cases).The duration of the development of the effect of enhancing the pigmentation of the iris is unknown. The iris discoloration seen with bimatoprost may be subtle over a period from several months to several years. The use of the drug has no effect on nevi or pigment deposits on the iris. Periorbital pigmentation has been reported to be reversible in some patients. A change in refraction is possible (due to the cancellation of therapy with miotic agents in some cases).The duration of the development of the effect of enhancing the pigmentation of the iris is unknown. The iris discoloration seen with bimatoprost may be subtle over a period from several months to several years. The use of the drug has no effect on nevi or pigment deposits on the iris. Periorbital pigmentation has been reported to be reversible in some patients. A change in refraction is possible (due to the cancellation of therapy with miotic agents in some cases).that the pigmentation of the periorbital region in some patients is reversible. A change in refraction is possible (due to the cancellation of therapy with miotic agents in some cases).that the pigmentation of the periorbital region in some patients is reversible. A change in refraction is possible (due to the cancellation of therapy with miotic agents in some cases).

Leather

Hair growth is possible in those areas of the skin to which the drug was accidentally applied. It is important to use the drug Bimoptic Plus strictly in accordance with the instructions for medical use and not to allow the drug to come into contact with the skin. Excipients The excipient benzalkonium chloride, which is part of the preparation, can cause irritation of the mucous membrane of the eyes and discoloration of soft contact lenses. Contact lenses must be removed before administration of the drug; they can be installed 15 minutes after instillation. Benzalkonium chloride can cause acute keratitis and / or toxic corneal ulcers. In this regard, it is necessary to monitor the patient's condition with frequent or prolonged treatment with Bimoptic Plus in persons with dry eye syndrome and with changes in the cornea.After opening the bottle, it is impossible to exclude the possibility of microbial contamination of its contents, which can lead to inflammatory lesions of the eyes. The shelf life of the drug after the first opening of the bottle is 28 days. After the specified time has elapsed, the bottle should be discarded, even if the solution has not been completely used. It is recommended to write down the date the bottle was opened on the cardboard box of the medicinal product.

Influence on the ability to drive vehicles and use mechanisms

There may be a transient deterioration in vision after administration of the drug, so the patient must wait until vision is completely restored before starting to drive vehicles and mechanisms.

Overdose

With the introduction of the drug Bimoptic Plus, an overdose is unlikely or may be associated with toxic effects. Bimatoprost In case of unintentional ingestion of a combination of bimatoprost + timolol, the following information may be useful: there were no symptoms of toxic effects of bimatoprost at doses up to 100 mg / kg / day during a 2-week oral administration in an experiment in rats and mice. The dose used in the study, expressed in mg / m2, exceeds 70 times the possible dose of bimatoprost if the contents of a vial containing a combination of bimatoprost + timolol are accidentally ingested by a child weighing 10 kg. Timolol Symptoms: in case of an overdose, bradycardia, a decrease in blood pressure, bronchospasm, headache, dizziness, shortness of breath, cardiac arrest may occur. Treatment: studies have shown that timolol is not completely excreted during hemodialysis.In case of an overdose, symptomatic therapy is performed.

Drug interactions

Special studies to study drug interactions of a fixed combination of bimatoprost + timolol have not been conducted. Potentiation of the effects of the combined use of ophthalmic solutions of beta-blockers and oral slow calcium channel blockers, guanethidine, beta-blockers, parasympathomimetics, antiarrhythmic drugs (including amiodarone) and cardiac glycosides, which was manifested by a decrease in blood pressure and / or severe bradycardia. It was reported about the potentiation of the systemic effects of beta-blockers (eg, decreased heart rate, depression) with the combined use of timolol with CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine). Periodically reported cases of mydriasis with the simultaneous use of ophthalmic beta-blockers and adrenaline (epinephrine). The patients,using the drug Bimoptic Plus with other analogs of prostaglandins should be monitored to control changes in intraocular pressure. Very rarely, cases of corneal calcification have been reported when combined with phosphate-containing eye drops in some patients with significant corneal damage.